Immunotherapy or depot medication (henceforth I/DM) programs that would prevent addiction or relapse to such drugs as tobacco or cocaine are largely unprecedented. These interventions differ in important respects from other pharmacological treatments for drug addiction and, for that matter, from vaccines used to prevent viral diseases. I/DMs may significantly alter the complex system of relationships among users, sellers, treatment providers, and social control agents. These actors are likely to change their behavior in both desirable and unintended ways.

Given the novelty of such interventions and uncertainty about how they might be implemented, it is not possible to forecast either the likelihood or the magnitude of unintended behavioral responses. Nevertheless, it is desirable to design I/DM interventions that might minimize such risks. This appendix identifies plausible mechanisms by which I/DMs might produce unintended consequences and reviews available evidence on the effects of these mechanisms in the research and clinical literatures on drug use and other risky behaviors. “Plausible” is defined here as something more than simply possible but not necessarily “more likely than not.”

Judgments about whether and how to implement I/DM programs should not necessarily be based solely on worst-case scenarios. Economists and risk analysts have long noted the opportunity costs in foregone benefits that can result from extreme risk aversion (e.g., Viscusi, 1992; cf.

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H
Anticipating Unintended Consequences of Vaccine-Like Immunotherapies and Depot Medications for Addictive Drug Use
Robert J. MacCoun
University of California, Berkeley
Immunotherapy or depot medication (henceforth I/DM) programs that would prevent addiction or relapse to such drugs as tobacco or cocaine are largely unprecedented. These interventions differ in important respects from other pharmacological treatments for drug addiction and, for that matter, from vaccines used to prevent viral diseases. I/DMs may significantly alter the complex system of relationships among users, sellers, treatment providers, and social control agents. These actors are likely to change their behavior in both desirable and unintended ways.
Given the novelty of such interventions and uncertainty about how they might be implemented, it is not possible to forecast either the likelihood or the magnitude of unintended behavioral responses. Nevertheless, it is desirable to design I/DM interventions that might minimize such risks. This appendix identifies plausible mechanisms by which I/DMs might produce unintended consequences and reviews available evidence on the effects of these mechanisms in the research and clinical literatures on drug use and other risky behaviors. “Plausible” is defined here as something more than simply possible but not necessarily “more likely than not.”
Judgments about whether and how to implement I/DM programs should not necessarily be based solely on worst-case scenarios. Economists and risk analysts have long noted the opportunity costs in foregone benefits that can result from extreme risk aversion (e.g., Viscusi, 1992; cf.

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Shrader-Frechette, 1991).1 But the literature on technological risks also documents the dangers posed by excessive optimism on the part of enthusiastic program designers (e.g., Janis, 1983; MacCoun, 1998a; Tenner, 1996; Vaughan, 1996). Thus, in the spirit of “devil’s advocacy,” it has been chosen in this appendix to err on the side of caution, giving greater attention to arguments in support of various unintended consequences than to possible counterarguments (which are nevertheless noted).
CONCEPTUAL FRAMEWORK
Program Prototypes
The committee has identified three types of immunotherapy or depot medication treatment protocols: overdose treatment, relapse prevention, and protection from addiction. Overdose treatment appears to be less susceptible than the other two categories to unintended consequences created by behavioral responses to the intervention, at least with respect to the mechanisms considered here. And to the extent that overdose treatment might operate via those mechanisms, its effects are likely to be similar to those of a relapse prevention program, only weaker. Thus, this appendix focuses primarily on relapse prevention and secondarily on the somewhat more remote prospect of addiction protection.
For simplicity the focus here is on interventions that target tobacco and cocaine use. Tobacco illustrates issues involved in pharmacological treatments for a legal, commercially available drug, and cocaine exemplifies issues posed for an illicit recreational drug.
Relevant Actors and Drug Use States
Psychoactive drug use is a multidimensional behavior characterized by many continuous parameters: age of onset, length of drug-use career, variety of drugs used, frequency of use, quantity consumed per use, and so on. To simplify the discussion, all this detail is abstracted away and drug use is characterized in terms of four mutually exclusive states. Figure H-1 presents a stochastic flow diagram, modified from a similar diagram used by Everingham and Rydell (1994). The figure depicts drug-using careers as patterns of movement among four “states”: never used, light use, heavy use, and former use. Among users, program participants are distinguished from nonparticipants and use of the target drug versus
1
The argument that risk-averse choices impose opportunity costs is analytical; the question of whether we should be more risk neutral is a value judgment.

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FIGURE H-1 Drug use conceptualized in terms of flows among four distinct drug use states.
use of other drugs. Behavioral effects on drug dealers, politicians, and the general public are also considered.
Presumably a relapse prevention program would target some fraction of heavy users. If effective, it should increase the flow of heavy users into nonuse and reduce the flow of nonusers back into use. An addiction protection program would target some fraction of light users and perhaps (not shown) newly heavy users and (more controversially) those at high risk who have never used. If effective, it should increase the flow of light users into nonuse and reduce the flow of nonusers into use.
In addition to these flows, it is important to consider the “stocks”—the distribution of individuals across these states. The distribution of consumption across users is strongly positively skewed for most drugs (see Everingham and Rydell, 1994; Skog, 1993)—though less dramatically so for tobacco than cocaine. As a result, the harmful consequences of substance use are not uniform but are disproportionately concentrated among the heaviest users.

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The relative viability of targeting the median user versus hard-core users in the right tail of the distribution will probably vary as a function of several factors (Edwards et al., 1994; MacCoun, 1998b; Rose, 1992). Everything else being equal, it will be more effective to target typical users when the dose-response curve for various harms rises very quickly with small doses and when typical users account for a large fraction of total consumption. It will be more effective to target heavy users when the dose-response curve for various harms rises slowly at low doses and when the statistical distribution of consumption is heavily skewed. Relapse prevention I/DMs would disproportionately target right-tail users; addiction protection I/DMs would presumably include individuals from the whole range of the use distribution (even including some who would never use anyway), depending on their recruitment process and our accuracy at predicting who is “at risk” for addiction. But of course the choice of users to target for a pharmacological intervention will also be determined by legal, ethical, economic, and political considerations not considered in this chapter.
Voluntary Versus Mandated Participation
The consequences of an I/DM program are likely to differ depending on whether participation is solely voluntary versus mandated by legal or other authorities (e.g., employers). The voluntary-mandatory distinction hinges in part on the legal status of the drug in question. MacCoun and Reuter (2001) and MacCoun, Reuter, and Schelling (1996) examine the effects of a drug’s legal status on its prevalence and harmful consequences. Here a few key points of relevance to the comparison of pharmacological interventions for a licit drug (e.g., tobacco) versus an illicit drug (e.g., cocaine) are summarized.
Prohibition almost certainly raises the price of a prohibited substance, probably substantially (MacCoun and Reuter, 2001; National Research Council, 2001; cf. Miron, 2003). This is one reason why cocaine users might be more likely than tobacco users to commit income-generating crimes, even in the absense of any pharmacologically mediated disinhibition or aggression.
Prohibited drugs are marketed quite differently from licit drugs; there is less quality control and far greater violence. The lack of quality control may make it more difficult to determine appropriate pharmacological dosages for cocaine addicts than for tobacco addicts. And the nature of black markets creates a risk that pharmacological interventions for illicit drugs might have nonpharmacological effects on violence.

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Prohibition increases the stigma associated with a drug, although stigma can have both desirable and undesirable consequences (see “Social Norm Effects” this appendix).
In addition to a drug’s legal status, a related consideration is whether participation in a pharmacological program would be voluntary or mandatory.2 Voluntary relapse prevention for either drug seems most feasible and would face few ethical and legal obstacles. For cocaine, mandatory participation would pose thorny ethical, legal, and political questions, but the drug’s illicit status makes such programs plausible (see National Research Council, 2001, Chapters 6 and 8 and Appendix E). On the other hand, mandatory participation in a relapse or addiction prevention seems implausible for tobacco, a licit drug.
Although the distinction between voluntary and mandatory programs has legal and political relevance, it may have less clinical and behavioral relevance. Many experts contend that mandatory treatment is as effective as voluntary treatment,3 and that conclusion seems even more plausible for these pharmacological interventions than for more traditional psychotherapeutic modalities. The behavioral mechanisms examined here seem as applicable to voluntary as to mandatory programs, given the severe self-control problems involved in drug addiction. Indeed, the very concept of “voluntariness” is problematic in the case of addictions, which are often characterized as “diseases of will” (see Elster and Skog, 1999; Vuchinich and Heather, 2003).
EFFECTS OF PRICE CHANGES
The first mechanism considered here involves the behavioral effects (on use and on criminality) of a change in drug prices brought about by I/DM programs.
2
The term “mandatory” is used here to refer to a program in which clients are required to participate under threat of formal legal sanctions. The term “coerced” is commonly used in the treatment literature but is ambiguous because many clients are “coerced” into treatment via the threat of informal sanctions—divorce, loss of a job, expulsion from school.
3
For evidence on this point, see Anglin and Hser (1990), Farabee, Prendergast, and Anglin (1998), Inciardi et al. (1997), Lawental et al. (1996), Maxwell (2000), Miller and Flaherty (2000), and Nishimoto and Roberts (2001). Manski et al. (2001) raise concerns about the methodologies used in these studies and also the possibility that mandated treatment has a “net-widening” effect on the scope of criminal justice activity.

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Price Elasticity of Demand
Some readers may question the relevance of a drug’s price for the behavior of a consumer who is addicted. Traditionally, many have assumed that addicts, by the very nature of their addiction, are oblivious to price changes; they will obtain their drug no matter what the cost, committing income-generating crime if need be to finance their habit. Thus, it has been surprising to learn that illicit drug use is in fact fairly sensitive to price variations.
Economists estimate sensitivity to prices in terms of the price elasticity of demand—the percentage change in consumption for a 1 percent change in price. Estimates for the price elasticity of cigarette demand are in the −0.3 to −0.5 range (Chaloupka and Pacula, 2000; Manning et al., 1991), suggesting that a 10 percent increase in the price of cigarettes would reduce overall consumption by only 3 to 5 percent. Thus tobacco users are in fact somewhat but not completely unresponsive to price. Cocaine users are more price sensitive; low estimates are around −0.4, but some studies find elasticities of −1.0 or more (see reviews by Caulkins and Reuter, 1996, and Chaloupka and Pacula, 2000). A drawback is that most estimates are based on users in the household population and may overrepresent casual users. But Reuter and Kleiman (1986) argue that, if anything, budget constraints tend to make heavy users more rather than less price sensitive. And Caulkins (2001) has shown that trends in emergency room incidents involving cocaine are highly responsive to trends in cocaine price, suggesting that heavy users are also price sensitive.
Assumptions Underlying a Shift in Demand
The analysis of drug price effects presented here is premised on four “best-case” assumptions about the effectiveness of I/DM programs. Later mechanisms will challenge each of these assumptions; to the extent that these assumptions are false, any price effects will probably be smaller than those contemplated here. Specifically, assume that: (1) targeted users cooperate fully with the intervention program; (2) the intervention completely discourages use of the target by program participants; (3) participants do not substitute other psychoactive drugs; and (4) the program has no direct effect on the behavior of nonparticipants, and any indirect effects are benign. Under these conditions, a successful psychopharmacological relapse or addiction prevention program ought to shift the demand curve downward, such that less cocaine (or tobacco) is demanded at any price. The magnitude of the demand shift would be determined by the number of users targeted and their previous levels of consumption.

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Effects Predicted by a Traditional Model of Supply and Demand
Figure H-2 presents a rudimentary “comparative statics” analysis of the implications of this shift in drug demand. In this type of micro-economic analysis, a product’s price and the quantity supplied are inferred from the equilibrium point where the supply curve (reflecting supplier responses) and the demand curve (reflecting consumer responses) intersect. Ceteris paribus, a downward shift in the demand curve ought to produce a reduction in the quantity supplied and a drop in the equilibrium price of the drug.4
In the short run, this reduced price should not in itself lead to increased use; by definition, the equilibrium price and quantity already reflect consumer and supplier preferences. But in the long run, reduced prices pose a risk of increased consumption, for two reasons. First, existing drug users may be more responsive to price changes over the long run than the short run (e.g., Reuter and Kleiman, 1986; Caulkins, 2001). Second, adolescents may be more likely to initiate use if they perceive the drug as inexpensive rather than expensive. This latter effect may be qualitative as well as quantitative; the reputation of a drug as “cheap” versus “expensive” can change over time. Compare cocaine’s reputation in the late 1970s versus the late 1980s.
On the other hand, a consequence of reduced cocaine demand is that any “psychopharmacological” criminality produced by the direct effects of the drug (Goldstein, 1985) should be reduced.5 Moreover, a price drop might reduce crime even among users not enrolled in an I/DM program. Presumably, some fraction of those nonparticipant cocaine users commit income-generating crimes to finance their use—what Goldstein calls “economic-compulsive” criminality. A reduction in price means that they might be expected to reduce their criminal involvement—a collateral benefit of a successful program. The effects of a price change on criminality, if any, will depend in part on whether the users who participate in I/DM programs differ from nonparticipants in their price sensitivity. If the two
4
Caulkins and Harwood each suggest that the I/DM effect could be modeled as a downward shift in the supply curve—supply reduction rather than demand reduction—in the sense that these treatments block the supply of drug to the brain. But it seems preferable to model the effects with respect to demand for two reasons. First, the supply function is usually conceptualized with respect to supplier behavior rather than consumer physiology or phenomenology. Second, I/DM programs, if effective, will reduce the demand of participants but will not necessarily affect the supply to nonparticipant users, at least not directly.
5
Of course, neither of these crime reduction benefits seems very likely for a tobacco program. Tobacco has not been causally linked with significant increases in psychopharmacological criminality, and because prices are lower (and the average user is more socially integrated), few users commit crimes to buy cigarettes.

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FIGURE H-2 Price and quantity decreases following a downward shift in demand, assuming a traditional supply curve.
NOTE: P1 = initial price, P2 = new price; Q1 = initial quantity supplied, Q2 = new quantity supplied.
classes of users differ, I/DM programs might alter the slope of the demand function by changing the composition of the remaining user pool.
Predicted Effects if the Supply Function Is Downward Sloping
The traditional analysis in Figure H-2 is plausible as a qualitative depiction of the tobacco market.6 But several experts (e.g., Kleiman, 1993;
6
Nevertheless, despite a substantial drop in demand, the non-tax price of tobacco has actually approximately doubled since 1985 (calculations for the author by Rosalie Pacula, senior economist at RAND, 11 November 2003). This increase is not fully understood, but it appears that the shift in the demand curve may have been accompanied by a shift in the supply curve, due to increased advertising expenses, tort litigation expenses, and other factors (personal communication to the author from Frank Chaloupka, University of Illinois at Chicago, 18 November 2003). It seems unlikely that an I/DM program for tobacco would have similar effects on supply costs.

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Reuter and Kleiman, 1986; Reuter et al., 1988; Rydell and Everingham, 1994) argue that the illicit nature of the cocaine business might produce a supply curve that is downsloping, as seen in Figure H-3. This conclusion follows if the marginal cost of producing a kilogram of cocaine does not increase with the total number of kilograms produced and the per-unit risk of seizures and other enforcement actions falls with the total quantity of cocaine that is produced. The assumption of a downward sloping cocaine supply curve is controversial (see Caulkins, Chiesa, and Everingham, 2000; National Research Council, 1999) but is important to consider because it has implications for the effect of a downward shift in the demand curve.
Figure H-3 indicates that with a downsloping supply curve a downward shift in the demand curve would still produce a reduction in the quantity supplied, but prices would actually rise. This is obviously a desirable effect if users not receiving an I/DM intervention are price sensitive because they can be expected to reduce their consumption even though they are not in the program. Moreover, the higher prices should discourage potential users from initiating drug use.
On the other hand, if those still using cocaine are relatively price insensitive, they might increase their rate of income-generating crime to
FIGURE H-3 Price increase and quantity decrease following a downward shift in demand, assuming a downsloping supply curve
NOTE: P1 = initial price, P2 = new price; Q1 = initial quantity supplied, Q2 = new quantity supplied.

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maintain their preferred level of consumption—clearly an unintended consequence of the program. This effect would be mitigated to the extent that those users targeted for the program were the ones most heavily involved in criminal activity—as might occur through a court-mandated program.
This discussion of price and criminality effects suggests the importance of additional empirical research on users’ responsiveness to price changes. To accurately predict the consequences of an I/DM intervention on drug markets, better information is needed on short- versus long-run price elasticities and on differences in the price sensitivity of likely participants versus other users.
NONPARTICIPATION AND NONCOMPLIANCE
The analysis of price effects presented above was premised on the best-case assumption that I/DM programs produce their intended shift in demand. The remaining mechanisms considered here each challenge that assumption. The simplest and least speculative challenge to the best-case scenario is the likelihood that some nontrivial fraction of targeted users will fail to participate.
It may be difficult to enroll targeted participants at high rates and sustain their participation for the desired length of time. In the Drug Abuse Treatment Outcome Study, a nationwide naturalistic examination of nonexperimental treatment settings, median retention in treatment ranged from 29 to 177 days across 18 long-term residential programs and from 42 to 144 days for 16 outpatient drug-free programs (Joe, Simpson, and Broome, 1998). Methadone clinics fared somewhat better, with a median of 117 to 583 days across 13 programs; across these programs, half of all clients participated for at least a year. But an examination of the evidence from a variety of at least partially analogous interventions suggests that high dropout rates are the norm.7
Evidence from Partially Analogous Programs
Smoking Cessation Programs
The smoking cessation evaluation literature has largely ignored the question of program attrition. For example, dropout rates are not ana-
7
These high dropout rates do not necessarily imply that those dropping out receive no treatment (see Simpson, Joe, and Brown, 1997) or do not stop using on their own (see Shadish et al., 1998); they simply suggest that high levels of participation in a vaccine program cannot be taken for granted.

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SOCIAL NORM EFFECTS
Another way that I/DM programs might influence drug use by non-program participants is by altering networks of social influence. One such effect is beneficial. A reduction in use by light users could have “social multiplier” effects on nonusers and current light users (see Caulkins et al., 1999). This follows under the assumption that current users socially reinforce, encourage, and facilitate use among those around them. There is much correlational evidence for this assumption, at least among adolescents (e.g., Elliott, Huizinga, and Ageton, 1985), although the correlation conflates a social influence effect with a selection effect, since high-risk peers tend to select each other as friends (Bauman and Ennett, 1996; Kandel, 1996).
But it is possible that this social influence effect would be inverted in the case of hard-core dependent users.12 Musto (1971/1987) and Johnston (1991) each offer versions of a “generational forgetting” model of drug epidemics, in which the increasing visibility of the deleterious effects of addiction triggers a reduction in initiation.13 Behrens and colleagues (1999, 2000, 2002) have incorporated this process into Everingham and Rydell’s (1994) model of the cocaine epidemic. Their analyses led to the disturbing prediction that if Musto and Johnston are correct, widespread drug treatment early in an epidemic could actually exacerbate it by slowing the social learning process. Similarly, if the generational forgetting model is correct, then ceteris paribus, reducing the visibility of the harms of addiction might reduce a social deterrent to drug use. This prediction is admittedly speculative. The generational forgetting model remains largely untested; there are simply too few “cycles” of data to test the cyclicity of drug epidemics. Still, this line of reasoning bolsters the concern that I/ DMs might well encourage drug use by reducing the perceived risks.
UNINTENDED EFFECTS ON DRUG MARKETING
Putting aside the unintended consequences discussed thus far, assume again for the sake of argument that a successful pharmacological intervention is widely implemented and reduces the prevalence and
12
Caulkins et al. (1999) included negative feedback from heavy use to initiation in their modeling of a social multiplier effect for primary prevention, but they concluded that the desirable multiplier effects would be larger than any negative effects.
13
In Musto’s account the predicted effect is cyclical because, as the number and visibility of users decline over time, initiation begins to rise again. The models developed by Behrens and colleagues (1999, 2000, 2002) allow for other possibilities (e.g., damped oscillation).

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severity of tobacco or cocaine addiction. This would almost certainly threaten the profitability of tobacco or cocaine production and sales. Producers and sellers, whether licit or illicit, may well respond in a compensatory fashion.
Illicit Drug Sellers
Sellers of cocaine or other targeted street drugs may respond in various ways. Drug sellers might move into the production and/or sales of other psychoactive drugs (e.g., Constantine, 1995; Thompson, 2002) or develop new synthetics that mimic the targeted drug without being blocked by I/DM pharmacologies. At least in the short run, dealers may act more aggressively to protect and expand their share of the diminishing market. There might be (at least temporarily) an upsurge in violence as sellers compete for a shrinking pool of addicts. Drug-selling organizations might also attempt to expand into regions where the relevant I/DM interventions are less available or less widely used. It has long been rumored that urban cocaine-trafficking organizations expanded into rural areas as urban drug enforcement became more aggressive in the 1990s (Butterfield, 2002; Johnson, 2003; National Alliance of Gang Investigators Associations, 2000; cf. Maxson, 1998).
The Tobacco Industry
If I/DM interventions against tobacco addiction were to become popular, the tobacco industry might also seek new users who are not currently targeted for these interventions (e.g., young people, rural communities, other nations) and seek to establish or strengthen these alternative markets. For example, as U.S. tobacco consumption has declined, tobacco companies have become more aggressive in international markets, especially in developing nations (World Health Organization, 2001). There might be new forms of advertising, perhaps subtly hinting that tobacco addiction is now a more manageable risk of their product.
The Pharmaceutical Industry
For manufacturers of immunotherapeuties or depot medications, the largest market will involve addiction protection rather than relapse prevention simply because the population of potential clients is so much larger. There are many more potential addicts than actual addicts, especially if “at risk” is defined broadly. (This is especially likely to be true for the tobacco market, which is roughly an order of magnitude larger than

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the market for illicit drugs other than marijuana.14) Many parents may feel a moral (or perhaps social) obligation to protect their children against the risk of future addiction. The industry might market the treatments in a manner that reinforces or amplifies this sense of responsibility.
Much may depend on the decision by public and private health insurance providers about whether to reimburse I/DM addiction protection and by any professional guidelines for off-label use established by professional medical societies (e.g., the American Medical Association). Broad coverage of youth addiction protection is likely to be socially inefficient. If parents and physicians define “addiction risk” too broadly, there will be a “moral hazard” problem of excessive utilization of the intervention. On the other hand, if insurers set strict limits on coverage (ex ante), they may face lawsuits if some youth who were denied coverage later became addicted.
UNINTENDED SOCIAL AND POLITICAL CONSEQUENCES
Again, assuming that a pharmacological intervention is widely implemented and is at least perceived to be successful in reducing addiction, other actors might also respond in unintended ways:
Nonusers may further stigmatize or ostracize smokers and drug users who have not availed themselves of a pharmacological relapse intervention. While this stigma may help to discourage initiation and escalation by casual users, the labeling theory tradition in sociology suggests that it could actually intensify the drug involvement of heavy users (MacCoun, 1993).
Law enforcement officials may demote cocaine offenses as an enforcement priority, increasingly viewing cocaine as a medical problem rather than a social control problem. This would be particularly troubling if these officials overestimated the actual “capture” or effectiveness rates of the pharmacological intervention.
Politicians and the general public may be less willing to actively support more traditional forms of treatment, primary prevention, and law enforcement. This would be particularly troubling if in fact a large fraction of existing users were ineligible for such a pharmacological intervention. Also, a reduction in support could have pernicious effects on substance abuse control efforts involving drugs for which no pharmacological intervention is available.
14
According to the National Household Survey on Drug Abuse, in 2001 there were 7 million current users of illicit drugs other than marijuana versus 66.5 million current users of a tobacco product. See http://www.samhsa.gov/oas/nhsda.htm#NHSDAinfo.

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There may be a political backlash against the coercive use (by legal authorities or parents) of this invasive technology. This seems particularly likely if mandated clients are disproportionately drawn from ethnic and racial minority groups, which is not implausible given the disproportionately high rates at which those groups are apprehended for drug use (MacCoun and Reuter, 2001).
CONCLUSIONS
This appendix raises a number of potential unintended consequences of a depot medication or immunotherapy program for addiction, including increased use of the target drug by some program clients (if the treatment is only partially effective and fails to reduce drug motivation, increased use of other drugs by program clients (a substitution effect), increased use of the target drug by those not in the program (through reductions in the perceived riskiness of the drug, and increased dealer violence (through increased competition for fewer customers and/or effects of the program on prices). There is little basis for estimating the likelihood of these potential outcomes other than to suggest that their probabilities are nontrivial (i.e., below 1.0 but closer to 0.50 than to 0).
Of course, these effects are not the only factors to consider when evaluating such a program. Even if all these consequences occurred, they may well be completely offset by the program’s benefits. A full analysis of the desirability of an I/DM program should consider other factors assessed elsewhere in this volume, including the ethical obligation to treat drug dependence if possible; the ethical, legal, and political objections to the intervention; the administrative and medical costs of the program; the cost effectiveness of the program relative to other interventions; and the program’s cost-benefit ratio. Nevertheless, the scenarios considered here are not implausible on their face. Each is based on familiar theoretical mechanisms, evidence from at least partially analogous interventions, or both. Program designers have an obligation to take these risks seriously and to minimize them through careful program implementation, monitoring, and evaluation.
ACKNOWLEDGMENTS
Helpful comments were received from Gantt Galloway, Rick Harwood, Mark Kleiman, Rosalie Pacula, Peter Reuter, Steve Sugarman, and especially Jon Caulkins.

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